Dr. Hesham Abboud of Case Western Reserve University School of Medicine and colleagues reviewed the safety and efficacy of current and emerging COVID-19 vaccines in MS patients, taking into consideration the impact of immunosuppressive or immunomodulatory disease-modifying therapies (DMTs).
In an email to Reuters Health, Dr. Abboud highlighted key findings of the review, published in the Journal of Neuroimmunology:
- Most COVID-19 vaccines are safe in MS patients. Immune-mediated neurological adverse events are rare and central demyelination has only been reported with the viral-vector vaccines (AstraZeneca, Johnson and Johnson).
- Inactivated virus (Sinopharm), RNA-based (Pfizer, Moderna), DNA-based (Inovio), and recombinant protein (Novavax) vaccines are expected to be safe in MS patients and, if available, are preferred over viral-vector vaccines.
- "The upcoming live-attenuated COVID-19 vaccine (Meissa) is either contraindicated or not preferred with MS DMTs for fear of enhanced virulence under the altered immune state," Dr. Abboud said.
- Beta interferons are not expected to impact vaccine efficacy. Normal or slightly altered vaccine efficacy can be expected with glatiramer acetate, teriflunomide, and natalizumab. Patients on dimethyl or diroximel fumarate are also expected to mount a normal immune response to the vaccine, he noted, as long as they have a normal lymphocyte count.
- Prior studies suggest that treatment with sphingosine 1-phosphate modulators (fingolimod, siponimod, ozanimod) can reduce cellular and humoral responses to vaccines.
"Treatment interruption prior to vaccination is not recommended because of the potential for severe MS rebound associated with the abrupt interruption of these agents," Dr. Abboud said. "Vaccination will still provide a partially protective response while taking these agents."
- Cell-depleting DMTs like rituximab, ocrelizumab, cladribine, and alemtuzumab can reduce vaccine efficacy, especially if the vaccine is received immediately after or before DMT dosing during maximum lymphocyte depletion. It is therefore advisable to complete vaccination at least four to six weeks before starting a cell-depleting DMT, or at least three to six months after the last dose in patients already on therapy.
- If possible, vaccination should be completed one month prior to the next DMT dose. Delaying the next dose to allow at least a four-week interval after vaccination should be considered in patients with stable disease and/or prolonged lymphocyte depletion.
"These concepts were recommended by the National MS Society and are in line with the recent case series published in Multiple Sclerosis and Related Disorders," Dr. Abboud said.
In that study, Dr. Diego Centonze of Vergata University in Rome and colleagues conclude, based on their experience with four patients, that timing of the vaccination, rather than lymphocyte count, may determine an MS patient's response to vaccination.
Two patients with low lymphocyte counts were taking cladribine and two were taking ocrelizumab. Three vaccinated three months from the last dose had a good immune response, but one patient (on ocrelizumab) did not develop appropriate antibody titers when vaccinated two months after the last medication dose.
Commenting on the case series, Dr. Abboud noted, "The authors did not factor in the differential impact of ocrelizumab on CD20-expressing T lymphocytes, neutrophils, total lymphocyte counts, and immunoglobulin levels in both patients. These important variables could have affected vaccine efficacy, in addition to timing."
Dr. Lauren Gluck, director of the Montefiore Multiple Sclerosis Center in New York City, told Reuters Health by email that, overall, she agrees with the findings of both studies. However, she noted, "One question that remains is how to define (vaccine administration) for the anti-CD20 drugs. These cause much lengthier, although specific, lymphocyte depletion, ranging from 6-12 months or longer."
"Providers have learned to approximate vaccine-timing recommendations based on studies like the VELOCE trial (https://bit.ly/2STZetr), " she said. "However, many patients on these drugs still have not generated antibodies to the COVID-19 vaccine even months after last infusion, particularly when they still have low CD20 levels. Ofatumumab poses a new challenge since it is dosed monthly. The best timing for vaccines with this drug is actively being studied."
"We have not seen statistically significant numbers of worse or different adverse outcomes in patients with MS," she added. "The COVID-19 vaccines are certainly less dangerous for patients with MS than the COVID-19 infection."
Dr. Centonze did not respond to requests for a comment.
SOURCES: https://bit.ly/2S0AHm8 Journal of Neuroimmunology, online May 4, 2021; and https://bit.ly/3oyQd52 Multiple Sclerosis and Related Disorders, online May 3, 2021.
By Marilynn Larkin
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